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https://hdl.handle.net/2440/118369
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Type: | Journal article |
Title: | The role of the copA copper efflux system in acinetobacter baumannii virulence |
Author: | Alquethamy, S.F. Khorvash, M. Pederick, V.G. Whittall, J.J. Paton, J.C. Paulsen, I.T. Hassan, K.A. McDevitt, C.A. Eijkelkamp, B.A. |
Citation: | International Journal of Molecular Sciences, 2019; 20(3):1-13 |
Publisher: | MDPI |
Issue Date: | 2019 |
ISSN: | 1661-6596 1422-0067 |
Statement of Responsibility: | Saleh F. Alquethamy, Marjan Khorvash , Victoria G. Pederick, Jonathan J. Whittall, James C. Paton, Ian T. Paulsen, Karl A. Hassan, Christopher A. McDevitt and Bart A. Eijkelkamp |
Abstract: | Acinetobacter baumannii has emerged as one of the leading causative agents of nosocomial infections. Due to its high level of intrinsic and adapted antibiotic resistance, treatment failure rates are high, which allows this opportunistic pathogen to thrive during infection in immune-compromised patients. A. baumannii can cause infections within a broad range of host niches, with pneumonia and bacteraemia being associated with the greatest levels of morbidity and mortality. Although its resistance to antibiotics is widely studied, our understanding of the mechanisms required for dealing with environmental stresses related to virulence and hospital persistence, such as copper toxicity, is limited. Here, we performed an in silico analysis of the A. baumannii copper resistome, examining its regulation under copper stress. Using comparative analyses of bacterial P-type ATPases, we propose that A. baumannii encodes a member of a novel subgroup of P1B-1 ATPases. Analyses of three putative inner membrane copper efflux systems identified the P1B-1 ATPase CopA as the primary mediator of cytoplasmic copper resistance in A. baumannii. Using a murine model of A. baumannii pneumonia, we reveal that CopA contributes to the virulence of A. baumannii. Collectively, this study advances our understanding of how A. baumannii deals with environmental copper toxicity, and it provides novel insights into how A. baumannii combats adversities encountered as part of the host immune defence. |
Keywords: | P-type ATPases P1B-1 bacterial metal ions virulence |
Rights: | © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
DOI: | 10.3390/ijms20030575 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1071659 http://purl.org/au-research/grants/nhmrc/1080784 http://purl.org/au-research/grants/nhmrc/1120298 http://purl.org/au-research/grants/nhmrc/1122582 http://purl.org/au-research/grants/nhmrc/GNT1159752 http://purl.org/au-research/grants/arc/FT170100006 http://purl.org/au-research/grants/arc/DP170102102 http://purl.org/au-research/grants/arc/DP150104515 |
Published version: | http://dx.doi.org/10.3390/ijms20030575 |
Appears in Collections: | Aurora harvest 8 Genetics publications |
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hdl_118369.pdf | Published version | 1.2 MB | Adobe PDF | View/Open |
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